Inflammation in Parkinson’s Disease: Causes and Consequences

Parkinson’s disease (PD) is the second most common progressive neurodegenerative disorder after Alzheimer’s disease (AD) with a prevalence of 0.5-1% among persons older than 65 years of age (Toulouse & Sullivan, 2008). The incidence increases to 2.6% in persons aged 85 and older, and has a mean age of onset of 55 years. Statistics released in 1990 from a unique global study carried out by the World Health Organisation, suggest that there are approximately 4 million PD patients worldwide. However, despite intensive research, the aetiology of this neurodegenerative disease still remains unclear and despite substantial efforts, a cure remains elusive. This, coupled with the increasing aging demographics, makes the importance of research into PD imperative, and the development of novel drug treatments a primary aim, both for economic and humanitarian purposes. The disease is a chronic, progressive neurodegenerative motor disorder, resulting in the selective loss of dopaminergic (DA) neurons within the substantia nigra (SN) pars compacta (pc) of the midbrain. As the disease progresses there is gradual circuitry degeneration within the nigrostriatal pathway, producing motor, cognitive and psychiatric symptoms (Braak et al., 2003). Lewy bodies are classified as the focal pathological hallmark of PD and their presence is necessary for the post-mortem diagnosis of the disease. They are not unique to PD however and are also found in other diseases such as dementia with Lewy Bodies and diffuse Lewy Body disease (Braak et al., 2003). PD can be further characterised by the presence of an accumulation of activated microglia within the SNpc (McGeer et al., 1988). PD exists in many forms and can be classified into both familial and idiopathic (also referred to as sporadic) forms, with epidemiological studies indicating approximately 5-10% of cases as being familial, and 90-95% as idiopathic (Tomiyama et al., 2008). Familial PD can be transmitted in an autosomal dominant (AD-PD) or recessive fashion (AR-PD). The study of genetic forms of PD has led to a better understanding of the underlying molecular mechanisms occurring during the disease progression. To date, six genes (SNCA, LRRK2, PRKN, DJ-1, PINK1 and ATP13A2) have been implicated in familial forms of PD (Bekris et al., 2010). In contrast to idiopathic PD, the genetic forms of this disease display a significantly younger age of onset and a shorter disease duration (Pankratz & Foroud, 2007). Despite this, patients with the autosomal dominant form of the disease have similar clinical and pathological features to those with idiopathic PD. In idiopathic PD, environmental factors such as toxins, free radicals and inflammation have been considered the most likely